The renewal of the Rochester Area Pepper Center (RAPC) builds on the experience of the previous 3 + years. The current RAPC's 2 intervention (IS) and 2 intervention development (IDS) studies focused on evaluating ways to improve or maintain the functional status of the elderly at various stages of physical dependency using standard exercise or pharmacologic interventions and pre- and post-treatment methods of functional assessment. Excellent progress has resulted in 23 publications from the IDs or IDSs, 93 from research of RAPC faculty, and 49 from work funded by the RDC. Despite past progress, the new proposal moves in a new direction. We will integrate basic mechanistic research into 3 clinical IDSs. IDS#1 extends our successful IS of Acute Respiratory Tract Infections (ARTI) in the frail elderly to determine if alterations in immunologic and thrombotic status are predisposers or contributors to, the functional decline noted in ARTI. IDS#2 builds on the current IS findings showing that resistance exercise training does not greatly improve myofibrillar protein synthesis in healthy elderly subjects. The new goal is to determine if a 'more youthful' rate of myofibrillar protein synthesis will result from gonadal steroid therapy thus minimizing the age-related skeletal muscle atrophy. In IDS#3 complementary approaches will be used to study the disease- or age-related declines in neural mechanisms governing spatial orientation and equilibrium control. These approaches include standing balance (postural control), eye-head and eye- head-hand coordination, and visual motion processing that distinguishes self- from externally -initiated movements. The goal is to clarify the parameters that maintain and influence sensory-motor integration between subject and environment. Research Development (RD), Research Resource ; [Biostatistics (RRB)], Demonstration and Information Dissemination (DID), and Administrative (LA) Cores contribute to all RAPC functions. The Cores a) provide seed money for new initiatives and to support the career development of junior faculty (RD); b) provide methods (RRA) for accurate assay of glutathione metabolism for the IDS and other ongoing research; c) assist in the experimental design and statistical analysis of data (RRB); d) inform the medical and lay communities of the RAPC's work and publicize its educational programs (DIDC); and e) provide the leadership, administrative structure and oversight (LA) needed to fulfill the goals of the IDS and Cores. The abiding principle in developing the new RAPC was that its studies and functions, relate and contribute to ongoing clinical and research programs at the U of R Medical Center thereby enhancing the Center's function and significance.